Nephrotoxic injury in fatal poisonings in children – etiology and pathological aspects

Introduction. The actual prevalence of toxic nephropathies in children is not fully known, because renal functional and structural changes caused by nephrotoxins are nonspecific. The objective of the study was to evaluate the aetiology and renal involvement in severe poisoning with lethal potential in children. Methods. We retrospectively analyzed a group of patients, aged between 0-18 years, with deaths due to acute intoxication, who were investigated at the National Institute of Legal Medicine “Dr. Mina Minovici” Bucharest, Romania, during a 9 years period. We analyzed the aetiology of deaths by poisoning in children, the aetiology and the frequency of nephrotoxic injury and the pathological aspects of nephrotoxic poisonings. Results. From a total of 69 children deaths due to acute intoxication, the most common cause of death was acute poisoning with carbon monoxide (23 cases). The other etiologies were represented by multidrug poisoning – 9 cases, organophosphorus intoxications – 9 cases, and intoxications with illicit drugs – 8 cases. Acute renal injury was present in 20 patients, mainly in acute multidrug poisoning. The most common aspect was tubular nephrosis in 15 cases, followed by the appearance of acute tubular necrosis in 10 cases, tubulo-interstitial nephritis in 1 case, and non-specific aspects with renal stasis in the remaining 6 cases. Conclusions. Kidney involvement in pediatric poisoning is rare, but when acute kidney injury occurs, the prognosis of the intoxication becomes severe. Renal injury was present in 30% of cases, either by direct kidney damage with acute tubular necrosis, or by association of haemodynamic, cardiogenic, or septic shock

Protocol for the EARCO Registry : a pan-European observational study in patients with α1-antitrypsin deficiency

Rationale and objectives Alpha-1 antitrypsin deficiency (AATD) is a genetic condition that leads to an increased risk of emphysema and liver disease. Despite extensive investigation, there remain unanswered questions concerning the natural history, pathophysiology, genetics and the prognosis of the lung disease in association with AATD. The European Alpha-1 Clinical Research Collaboration (EARCO) is designed to bring together researchers from European countries and to create a standardised database for the follow-up of patients with AATD. Study design and population The EARCO Registry is a non-interventional, multicentre, pan-European, longitudinal observational cohort study enrolling patients with AATD. Data will be collected prospectively without interference/modification of patient's management by the study team. The major inclusion criterion is diagnosed severe AATD, defined by an AAT serum level <11 µM (50 mg·dL−1) and/or a proteinase inhibitor genotype ZZ, SZ or compound heterozygotes or homozygotes of other rare deficient variants. Assessments at baseline and during the yearly follow-up visits include lung function testing (spirometry, body plethysmography and diffusing capacity of the lung), exercise capacity, blood tests and questionnaires (symptoms, quality of life and physical activity). To ensure correct data collection, there will be designated investigator staff to document the data in the case report form. All data will be reviewed by the EARCO database manager. Summary The EARCO Registry aims to understand the natural history and prognosis of AATD better with the goal to create and validate prognostic tools to support medical decision-making

Cardiovascular diseases and air pollution in Novi Sad, Serbia

Objectives: A large body of evidence has documented that air pollutants have adverse effect on human health as well as on the environment. The aim of this study was to determine whether there was an association between outdoor concentrations of sulfur dioxide (SO2) and nitrogen dioxide (NO2) and a daily number of hospital admissions due to cardiovascular diseases (CVD) in Novi Sad, Serbia among patients aged above 18. Material and Methods: The investigation was carried out during over a 3-year period (from January 1, 2007 to December 31, 2009) in the area of Novi Sad. The number (N = 10 469) of daily CVD (ICD-10: I00-I99) hospital admissions was collected according to patients' addresses. Daily mean levels of NO2 and SO2, measured in the ambient air of Novi Sad via a network of fixed samplers, have been used to put forward outdoor air pollution. Associations between air pollutants and hospital admissions were firstly analyzed by the use of the linear regression in a single polluted model, and then trough a single and multi-polluted adjusted generalized linear Poisson model. Results: The single polluted model (without confounding factors) indicated that there was a linear increase in the number of hospital admissions due to CVD in relation to the linear increase in concentrations of SO2 (p = 0.015; 95% confidence interval (95% CI): 0.144-1.329, R2 = 0.005) and NO2 (p = 0.007; 95% CI: 0.214-1.361, R2 = 0.007). However, the single and multi-polluted adjusted models revealed that only NO2 was associated with the CVD (p = 0.016, relative risk (RR) = 1.049, 95% CI: 1.009-1.091 and p = 0.022, RR = 1.047, 95% CI: 1.007-1.089, respectively). Conclusions: This study shows a significant positive association between hospital admissions due to CVD and outdoor NO2 concentrations in the area of Novi Sad, Serbia

Is diet partly responsible for differences in COVID-19 death rates between and within countries?

Correction: Volume: 10 Issue: 1 Article Number: 44 DOI: 10.1186/s13601-020-00351-w Published: OCT 26 2020Reported COVID-19 deaths in Germany are relatively low as compared to many European countries. Among the several explanations proposed, an early and large testing of the population was put forward. Most current debates on COVID-19 focus on the differences among countries, but little attention has been given to regional differences and diet. The low-death rate European countries (e.g. Austria, Baltic States, Czech Republic, Finland, Norway, Poland, Slovakia) have used different quarantine and/or confinement times and methods and none have performed as many early tests as Germany. Among other factors that may be significant are the dietary habits. It seems that some foods largely used in these countries may reduce angiotensin-converting enzyme activity or are anti-oxidants. Among the many possible areas of research, it might be important to understand diet and angiotensin-converting enzyme-2 (ACE2) levels in populations with different COVID-19 death rates since dietary interventions may be of great benefit.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Intragastric balloon: is there any place left for It in the treatment of obesity?

Intragastric balloon (IGB) is used in the treatment of obesity for more than 20 years, both as a self-standing procedure and as a bridge treatment to bariatric surgery. The indications and results are well known, due to its characteristics as a non-surgical, endoscopic, minimally invasive and temporary treatment. Recently new models of IGB appeared on the market, and FDA approved for the first time in 2015 two models as treatment of obesity in the United States. Spatz™ Adjustable Balloon System is the first adjustable IGB, tolerated for 12 months, available from 2005. Between 2013-2015 thirty overweighted/obese patients were treated with Spatz3™, maintained in place for approximately 12 months, with a minimum follow-up of 6 months. The results, complications and efficacy of the Spatz3™ balloon are presented, together with an extended review of the literature. IGB represents a useful tool in the treatment of obesity, when patient’s selection is careful done